Different batches of atorvastatin, represented by two immediate release formulation designs, were studied using a novel dynamic dissolution apparatus, simulating stomach and small intestine. A universal dissolution method was employed which simulated the physiology of human gastrointestinal tract, including the precise chyme transit behavior and biorelevant conditions. The multicompartmental dissolution data allowed direct observation and qualitative discrimination of the differences resulting from highly pH dependent dissolution behavior of the tested batches. Further evaluation of results was performed using IVIVC/IVIVR development. While satisfactory correlation could not be achieved using a conventional deconvolution based-model, promising results were obtained through the use of a nonconventional approach exploiting the complex compartmental dissolution data.

Department of Applied Pharmacy Faculty of Pharmacy University of Veterinary and Pharmaceutical Sciences Brno Palackého 1 3 612 42 Brno Czech Republic

Department of Chemical Drugs Faculty of Pharmacy University of Veterinary and Pharmaceutical Sciences Brno Palackého 1 3 612 42 Brno Czech Republic ; Department of Internal Medicine Hematology and Oncology Faculty of Medicine Masaryk University Kamenice 5 625 00 Brno Czech Republic

Department of Pharmaceutical Technology and Biopharmaceutics Faculty of Pharmacy Jagiellonian University Medical College Medyczna 9 Street 30 688 Kraków Poland

Department of Pharmacoepidemiology and Pharmacoeconomics and Department of Social Pharmacy Faculty of Pharmacy Jagiellonian University Medical College Medyczna 9 Street 30 688 Kraków Poland ; Simcyp Limited Blades Enterprise Centre John Street Sheffield S2 4SU UK

Zobrazit více v PubMed

McAllister M. Dynamic dissolution: a step closer to predictive dissolution testing? Molecular Pharmaceutics. 2010;7(5):1374–1387. doi: 10.1021/mp1001203. PubMed DOI

Culen M., Dohnal J. Advances in dissolution instrumentation and their practical applications. Drug Development and Industrial Pharmacy. 2013 PubMed

Souliman S., Beyssac E., Cardot J.-M., Denis S., Alric M. Investigation of the biopharmaceutical behavior of theophylline hydrophilic matrix tablets using usp methods and an artificial digestive system. Drug Development and Industrial Pharmacy. 2007;33(4):475–483. doi: 10.1080/03639040601128654. PubMed DOI

Amidon G. L., Lennernas H., Shah V. P., Crison J. R. A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharmaceutical Research. 1995;12(3):413–420. doi: 10.1023/A:1016212804288. PubMed DOI

Bárta J., Mudra P., Pešek V., et al. Digestive tract simulator. 2011, http://patentscope.wipo.int/search/en/WO2011069472.

Culen M., Rezacova A., Jampilek J., Dohnal J. Designing a dynamic dissolution method: a review of instrumental options and corresponding physiology of stomach and small intestine. Journal of Pharmaceutical Sciences. 2013;102(9):2995–3017. doi: 10.1002/jps.23494. PubMed DOI

Watanabe T., Kusuhara H., Maeda K., et al. Investigation of the rate-determining process in the hepatic elimination of HMG-CoA reductase inhibitors in rats and humans. Drug Metabolism and Disposition. 2010;38(2):215–222. doi: 10.1124/dmd.109.030254. PubMed DOI

Ishigami M., Honda T., Takasaki W., et al. A comparison of the effects of 3-hydroxy-3-methylglutaryl-coenzyme a (HMG-CoA) reductase inhibitors on the CYP3A4-dependent oxidation of mexazolam in vitro. Drug Metabolism and Disposition. 2001;29(3):282–288. PubMed

Jacobsen W., Kuhn B., Soldner A., et al. Lactonization is the critical first step in the disposition of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor atorvastatin. Drug Metabolism and Disposition. 2000;28(11):1369–1378. PubMed

Kim J.-S., Kim M.-S., Park H. J., Jin S.-J., Lee S., Hwang S.-J. Physicochemical properties and oral bioavailability of amorphous atorvastatin hemi-calcium using spray-drying and SAS process. International Journal of Pharmaceutics. 2008;359(1-2):211–219. doi: 10.1016/j.ijpharm.2008.04.006. PubMed DOI

Mendyk A. CRAN—Package Rivivc. http://cran.r-project.org/web/packages/Rivivc/index.html.

Jamei M., Marciniak S., Edwards D., et al. The simcyp population based simulator: architecture, implementation, and quality assurance. Silico Pharmacology. 2013;1(1):p. 9. PubMed PMC

Poulin P., Theil F.-P. Prediction of pharmacokinetics prior to in vivo studies. 1. Mechanism-based prediction of volume of distribution. Journal of Pharmaceutical Sciences. 2002;91(1):129–156. doi: 10.1002/jps.10005. PubMed DOI

Lennernäs H., Aarons L., Augustijns P., et al. Oral biopharmaceutics tools—time for a new initiative—an introduction to the IMI project OrBiTo. European Journal of Pharmaceutical Sciences. 2014;16(57):292–299. doi: 10.1016/j.ejps.2013.10.012. PubMed DOI

FDA. Guidance for Industry: Extended Release Oral Dosage Forms: Development, Evaluation, and Application of in Vitro/in Vivo Correlations. 1997. PubMed

Lennernäs H. Clinical pharmacokinetics of atorvastatin. Clinical Pharmacokinetics. 2003;42(13):1141–1160. PubMed

Exploration of Neusilin® US2 as an Acceptable Filler in HPMC Matrix Systems-Comparison of Pharmacopoeial and Dynamic Biorelevant Dissolution Study

Optimization of Dissolution Compartments in a Biorelevant Dissolution Apparatus Golem v2, Supported by Multivariate Analysis